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• Transcriptomic analysis of LINE1 expression in the human brain

  Twist Biosciences probes were designed to enrich LINE1 and HERV sequences from human brain cDNA libraries. Postmortem human prefrontal cortex and temporal cortex samples from non-diseased controls and Alzheimer's disease were used. Enriched cDNA libraries were sequenced on a PacBio Sequel II (15-16 samples per SMRTCell).

  Study EGAS50000000184

• Ex vivo modeling of precision immuno-oncology responses in lung cancer

  Single-cell RNA-sequencing (scRNA-seq) data from paired lung cancer organoids and immune cells. The experiment was performed using the Single Cell 5' solution of 10X Genomics. The dataset includes 15 samples from 4 multiplexed experiments. The multiplexing was performed using the Feature Barcoding technology of 10X Genomics.

  Study EGAS50000000593

• Identifying rare genetic variants in 21 highly multiplex autism families

  Study EGAS00001006928

• scRNA-seq data of Anti-Her2-CAR T cells treated with immunomodulatory metabolites

  Anti-Her2-CAR T cells produced from T cells derived from healthy human donors were treated with DMSO (control) or either of the immunomodulatory metabolites indole‐3‐carboxaldehyde (ICA), valeric acid (VA) and isovaleric acid (IVA) to assess effects on CAR T cell function. scRNA-seq libraries were generated on a 10X Chromium controller with On-Chip-Multiplexing. The individual samples in a library are distinguished during analysis on the single-cell level via the cell barcode class.

  Dataset EGAD50000002012

• WGS data of conditional knockout mouse model mammary tumours

  Deposited here are 56 whole-genome sequencing BAM files from 15 Trp53f/w, 12 Trp53f/f, 14 Brca1f/f Trp53f/w, and 15 Brca1f/f Trp53f/f mouse mammary tumor samples sequenced on Illumina NovaSeq PE150. An additional 6 whole genome sequencing BAM files from corresponding normal tissues of mice are also included as controls (BPC_D666, B1PC_D840, BPTC_D992, PC_D503, PC_D720_Kid, PTC_H531). All samples were used in the study “Insights into BRCA1 and TP53 associated breast cancer development from integrated whole genome analysis of mouse model mammary tumors, Huo et al., 2026.”

  Dataset EGAD50000002036

• Whole-genome sequencing data of poorly differentiated thyroid carcinomas and matched blood from six patients

  This dataset contains raw sequencing reads in FASTQ format from 12 samples, comprising paired tumour and matched blood DNA from six patients diagnosed with poorly differentiated thyroid carcinoma (PDTC). Genomic DNA was extracted from fresh-frozen tumour tissue and peripheral blood using standard protocols. Whole-genome sequencing was performed on the Illumina HiSeq X Ten platform, generating paired-end reads at an average depth of approximately 20X. These data support investigations into the somatic mutational landscape and genomic alterations associated with PDTC.

  Dataset EGAD50000001628

• NGS-Based Mutational Analysis of 87 PMBL Patients from the GAINED Cohort (Subset of 382 Sequenced Patients)

  Targeted DNA sequencing was performed on DNA extracted from 87 formalin-fixed paraffin-embedded (FFPE) samples, representing a subset of the 382 sequenced patients from the GAINED cohort. A custom “Lymphopanel” was used to identify mutations in 70 genes associated with lymphomagenesis. Library preparation, exome capture, sequencing, and analysis were conducted by IntegraGen SA (Evry, France). Sequencing was performed on an Illumina HiSeq4000 platform, with variant calling and annotation using established bioinformatics tools such as MuTect and VEP.

  Dataset EGAD50000001359

• CITEseq data of Reactive Lymph Nodes

  Mononuclear cells were isolated as cell suspensions by dissociation in a BD Horizon™ Dri Tumor & Tissue Dissociation Reagent (BD Biosciences) using a gentleMACS dissociator (Miltenyi Biotec). A totalseq-C antibody cocktail (Biolegend) was used, and the cell suspensions were diluted to a concentration of 1,000 cells/μL. Library sequencing was performed using the NovaSeq6000 System (Illumina). The FASTQ files were aligned to the 10x provided reference genome using 10x Genomics Cell Ranger software v7.1.0 to create unique molecular identifier count tables of gene expression of the samples.

  Dataset EGAD50000000538

• Multiple paralogues and recombination mechanisms contribute to the high incidence of 22q11.2 Deletion Syndrome

  The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion disorder. Why the incidence of 22q11.2DS is much greater than that of other genomic disorders remains unknown. Short read sequencing cannot resolve the complex segmental duplications (SDs) to provide direct confirmation of the hypothesis that the rearrangements are caused by non-allelic homologous recombination between the low copy repeats on chromosome 22 (LCR22s). To enable haplotype-specific assembly and rearrangement mapping in LCR22 clusters, we used whole genome (ultra-)long read sequencing of 9 duos (patients and parent of origin).

  Dataset EGAD50000000855

• RNA sequencing of pretreatment, on-treatment and posttreatment gastric and gastroesophageal junction tumors treated with neoadjuvant anti-PD-L1 plus chemotherapy

  This set contains a total of 78 files cram files with RNA sequencing data from 20 patients included in the PANDA study treated with 1 cycle of monotherapy atezolizumab and 4 cycles atezolizumab plus chemotherapy (docetaxel, oxaliplatin and capecitabine). RNA was isolated from fresh frozen material and sequenced at 4 timepoints baseline, after monotherapy atezolizumab, after combination atezolizumab plus chemotherapy and at resection (due to 2 missing samples, there is a total of 78 samples).

  Dataset EGAD50000000241

• NGS-based monitoring of the T cell receptor repertoire in living donor kidney transplant patients undergoing combination cell therapy

  PBMCs from six kidney transplant recipients receiving as part of the Trex001 study autologous Tregs and donor bone marrow and six control patients not receiving either of the two treatments were collected pre-transplant and at one, three and six month post-transplant. Donor reactive T-cells were identified by mixed lymphocyte reactions (MLR) and lineage specific T-cell receptor (TCR) repertoires of native T-cells and proliferating and non-proliferating T-cells from MLRs were determined by next generation sequencing based profiling of the TCR.

  Dataset EGAD50000000302

• ctgap-G-1

  Illumina HumanCoreExome-12v1-1_A chip typing in a Greek adolescent population

  Dataset EGAD00010001005

• EGAD00010000516

  Samples from the Pomak Villages in Greece, Pomak isolate

  Dataset EGAD00010000516

• Transcriptome profiling of HNSCC treated with PD1/PDL1

  Immune checkpoint inhibitors have improved survival in several solid tumors, including head and neck squamous cell carcinoma (HNSCC). However, current use of PD-1/PD-L1 inhibitors relies on PD-L1 expression, which does not reliably predict patient response. Therefore, better predictive biomarkers are needed to identify which patients benefit from immunotherapy. Previous studies suggest that genomic and transcriptomic features may help predict treatment response. This study aims to integrate genomic, transcriptomic, and methylomic data from 31 patients with recurrent/metastatic HNSCC to identify new biomarkers of resistance to anti-PD-1/PD-L1 therapy.

  Dataset EGAD50000002506

• Comprehensive Genomic Profiling of a National Cohort of Pediatric Papillary Thyroid Carcinoma in Hungary

  Pediatric papillary thyroid carcinoma (PTC) is a rare childhood malignancy with increasing incidence and distinct clinicopathological features, including high rate of locoregional metastases and different molecular background compared to adult cases. Traditional treatments (surgery, radioactive iodine) are effective but pose long-term risks, prompting the exploration of targeted therapies. We performed comprehensive genomic profiling on 21 pediatric PTC patients applying Illumina TruSight Oncology 500 platform and detected mutations, gene fusions, copy number variations and revealed tumor mutational burden.

  Dataset EGAD50000002659

• DNA-seq BAM files from 16 patients affected by acute intermittent porphyria

  Paired-end BAM files from 16 patients affected by acute intermittent porphyria. Whole genome sequencing of these samples was performed in an Illumina HiSeq 4000 instrument. Libraries were prepared using the Fisher PE Kit (Kapa Biosystems). FASTQ files were processed at the CNAG (Barcelona) using the GEM short-read aligner on the human genome version hs37d5, producing a total of 16 BAM files.

  Dataset EGAD00001006951

• Hypothalamic transcriptome in Prader-Willi syndrome

  Transcriptional analysis of brain tissue from people with molecularly defined causes of obesity may highlight novel disease mechanisms and therapeutic targets. Prader-Willi syndrome (PWS) is a genetic obesity syndrome characterised by severe hyperphagia. We performed RNA sequencing of the hypothalamus from 4 individuals with PWS and 4 age-matched controls.

  Study EGAS00001002901

• Identification of causal mutation in two patients with Sotos Syndrome Features

  We performed whole exome sequencing (WES) on genomic DNA derived from two patients with Sotos Syndrome Features. Sequencing (100 base pair paired-end) was performed on an Illumina Hiseq 2000 sequencer after enrichment of 62Mb of exonic and adjacent intronic sequences with TruSeq Exome Enrichment Kit (Illumina, San Diego, CA, USA).

  Study EGAS00001000993

• Evaluating the immune response in treatment-naive hospitalised patients with influenza and COVID-19

  Clinical characteristics and peripheral blood were acquired upon hospital admission from two well characterised cohorts, a cohort of patients infected with influenza and a cohort of patients infected with SARS-CoV-2 during the first wave of the pandemic and prior to availability of COVID-19 treatments and vaccines.

  Study EGAS00001005971

• Cambridge COVID-19 Single-cell PBMC

  Single-cell multi-omic profiling of healthy controls, asymptomatic and hosptial-admitted COVID19 patients recruited from Addenbrookes and Royal Papworth hospitals, in collaboration with the NIHR Cambridge Bioresource. Data represent RNA-seq, surface protein measurements (CITE-seq) of 192 antibody targets, along with VDJ-seq profiling of single T cell and B cell receptors. Samples are pooled, with 4 donors per pool. Germ-line genotypes are provided (VCF) to aid demultiplexing of single-cell and assignment to specific patient donor samples.

  Dataset EGAD00001007867

• WGS of exposed organoids

  The mutagenicity of bacteria was assessed by serially exposing human small intestinal organoids to various bacterial species or isolated toxins. We have used the following abbreviations: EWT: Organoids exposed to E. coli described in PMID: 32106218 EKO: Organoids exposed to isogenic E. coli as EWT, with knockout of the deltaClbQ gene, rendering them unable to produce colibactin DYE: Organoids exposed to FastGreen injection control dye NIS: Organoids exposed to E. coli Nissle ETBF: Organoids exposed to the protease toxin BTF produced by ETBF-bacteria.

  Dataset EGAD00001008687

• RNA-seq Revision

  The dataset comprises bulk RNA‑seq libraries generated on the Illumina NextSeq 500 platform, including primary human hepatocytes (four donors), colon tissue (four masked replicates), and a comprehensive set of iPSC‑derived samples from the JHU106, ChiPSC18, ChiPSC22, and H9 lines. The collection covers multiple differentiation stages from iPSC to DE to HLC and cultivation protocols (CEL, HAY, SPH) with at least three replicates per condition. All sequencing data are provided as raw FASTQ files, with colon samples delivered as masked FASTQ in accordance with patient consent requirements.

  Dataset EGAD00001008951

• Hubrecht Organoid Technology Colon Cancer Study

  Functional screening on patient-derived organoids identifies a therapeutic bispecific antibody that triggers EGFR degradation in LGR5+ tumor cells

  Dataset EGAD00001008445

• Healthy control and lung cancer plasma cfDNA samples from various collection tubes

  The dataset contains 6 lung cancer and 60 healthy control plasma cfDNA samples collected in EDTA, PAXGene and Norgen blood collection tubes at various locations. Shallow WGS was performed on an Illumina Novaseq S4 PE150bp. Samples are provided as raw reads without any prior processing.

  Dataset EGAD00001008322

• Whole-exome sequencing laser capture micro-dissected biopsies of human renal cell carcinoma

  The dataset comprises whole exome sequences from laser capture micro-dissected biopsies of 10 patients diagnosed with clear cell renal cell carcinoma. In total over 100 regions are sampled to allow 'focally exhaustive' sequencing and explore the limits of intra-tumoural heterogeneity.

  Dataset EGAD00001008029

• 79 Human Hearts snRNAseq

  Using single-nucleus RNA sequencing, we characterized the transcriptome of 880,000 nuclei from 18 control and 61 failing, nonischemic human hearts with pathogenic variants in DCM and ACM genes or idiopathic disease.

  Dataset EGAD00001009292

• Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA dataset

  Whole-exome sequencing of tumour regions and deep targeted sequencing of plasma samples.

  Dataset EGAD00001010031

• T-cell receptor targeting FLT3 D835Y mutation study

  We identified a T-cell receptor (TCR) reactive to the recurrent FLT3 D835Y mutation in the tyrosine-kinase domain. To validate the elimination efficacy of leukemia cells, we transplanted human acute myeloid leukemia (AML) cells with FLT3 D835Y mutations into NSG-SGM3 mice and treated either with TCR FLT3 D835Y redirected T cells, or control TCR (TCR 1G4). After treatment, we performed flow sorting of AML blasts (CD3-CD19-) and primary T cells (CD3+CD8+orCD4+CD19-CD33-) and performed whole-exome sequencing.

  Dataset EGAD00001011258

• Whole Exome sequencing of Gingivo-buccal Cancer - ICGC India Project Batch04

  This dataset pertains to whole exome sequencing of paired DNA samples of Gingivo-buccal oral cancer patient.DNA was isolated from the tumor and blood tissues of 47 patients (94 samples).We have performed Nextera exome capture and sequenced exome libraries in Illumina HiSeq platform.We have uploaded BWA-ALN aligned BAM files.

  Dataset EGAD00001003987

• Chronic lymphocytic leukemia driven by paradoxical ERK activation during BRAF inhibitor treatment

  Whole-exome sequencing of a chronic lymphocytic leukemia (CLL) developed during vemurafenib treatment of a patient with malignant melanoma. Peripheral blood mononuclear cells were separated by Ficoll gradient centrifugation. DNA was extracted from highly purified (>97%) CD19+CD5+ cells obtained from the patient while being under BRAF inhibition versus CD14+ germline control cells (>90% purity). No alterations that could be linked to aberrant RAS activity or paradoxical RAF/MEK/ERK signaling could be identified in the CLL, which shows characteristic copy number alterations.

  Dataset EGAD00001000997

• Chondromyxoid fibroma

  Chondromxoid fibroma is a benign tumour of bone with unknown underlying pathogenesis. To determine pathognomic genomic event in chondromyxoid fibroma whole genome sequencing will be undertaken to reconstruct rearrangements and find underlying mutations.

  Dataset EGAD00001001063

• African American Breast Cancer GWAS

  The GWAS includes African American participants from 9 epidemiological studies of breast cancer, comprising a total of 3,153 cases and 2,831 controls (cases/controls: The Multiethnic Cohort Study (MEC), 734/1,003; The Los Angeles component of The Women's Contraceptive and Reproductive Experiences (CARE) Study, 380/224; The Women's Circle of Health Study (WCHS), 272/240; The San Francisco Bay Area Breast Cancer Study (SFBCS), 172/231; The Northern California Breast Cancer Family Registry (NC-BCFR), 440/53;The Carolina Breast Cancer Study (CBCS), 656/608; The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Cohort, 64/133; The Nashville Breast Health Study (NBHS), 310/186; and, The Wake Forest University Breast Cancer Study (WFBC), 125/153). Quality control of the GWAS data and additional details can be found in Chen et al. Hum Genet. 2013 (PMID: 22923054)

  Study phs000851

• Molecular Basis of Neuroendocrine Prostate Cancer (Trento/Cornell/Broad 2015)

  A subset of advanced prostate cancers can progress from an androgen receptor (AR)-driven state to AR independence, often associated with low or absent AR expression and extensive neuroendocrine differentiation. Once neuroendocrine prostate cancer (NEPC) develops, patients typically demonstrate an aggressive clinical course and poor overall survival. Early diagnosis is important but remains challenging as the clinical and pathologic features associate with AR independence and NEPC are poorly defined. We performed whole exome sequencing of 114 metastatic tumors from 81 patients (35 with morphologic features of NEPC). Serial or synchronous samples were included to characterize heterogeneity and the transition from adenocarcinoma to NEPC. Computational analysis of clonality and allele specific quantification were performed using CLONET. Quantitative mRNA assessment including AR signaling genes and DNA methylation were evaluated in the context of genomic changes.

  Study phs000909

• Single-Cell Multi-Omic Analysis of the Vestibular Schwannoma Ecosystem Uncovers a Nerve Injury-Like State

  Vestibular schwannomas are benign tumors that can lead to significant morbidity, including hearing loss, facial nerve paralysis and obstructive hydrocephalus. The genomic landscape of vestibular schwannomas is relatively bland and the molecular pathophysiology of vestibular schwannomas is poorly understood. Therefore, we performed single cell RNA sequencing on 15 sporadic vestibular schwannomas, with paired single cell ATAC sequencing (n = 6) and whole exome sequencing (n = 12) to perform a detailed characterization of the vestibular schwannoma tumor microenvironment at the transcriptional and epigenetic level. We validated our results by analyzing bulk RNA sequencing data from 22 newly sequenced vestibular schwannomas and 173 previously sequenced bulk RNA sequencing data from 195 vestibular schwannomas. Data available in dbGaP include whole exome sequencing of 12 tumors and matched blood samples. Matching single cell RNA sequencing and single cell ATAC sequencing data is available via NCBI GEO.

  Study phs003318

• Multiplexed scRNA-Seq Reveals Cellular and Genetic Correlates of SLE

  Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Knowledge of circulating immune cell types and cell states associated with SLE remains incomplete. We profiled over 1.2 million PBMCs (160 cases, 98 controls) with multiplexed single-cell RNA-seq (mux-seq). Cases exhibited prominent expression of type-1 interferon-stimulated genes (ISG) in monocytes, reduction of naïve CD4+ T cells that correlated with monocyte ISG expression, and expansion of repertoire-restricted cytotoxic GZMH+ CD8+ T cells. Cell-type-specific expression features accurately predicted case-control status and stratified patients into two molecular subtypes. We integrated dense genotyping data, mapping cell-type-specific cis-eQTLs and linked known and novel SLE-associated variants to cell-type-specific gene expression. These results demonstrate mux-seq as a systematic approach to characterize cellular composition, identify transcriptional signatures, and annotate genetic variants associated with SLE.

  Study phs002812

• End motifs analysis of circulating DNA from the plasma of patients with stage II-III breast cancer (n=50), stage I-III non-small cell lung cancer (n=56), metastatic colorectal cancer (mCRC) (n=15) and healthy individuals (n=37)..

  We have developed an algorithm designed to discriminate cancer patients and healthy individuals based on cirDNA fragment end motif analysis assisted by machine learning, using data obtained from shallow whole genome sequencing (a method we call EMA). We applied EMA to cirDNA from the plasma of patients with stage II-III breast cancer, stage I-III non-small cell lung cancer, and metastatic colorectal cancer (mCRC). CirDNA from 158 individuals was prepared following the conventional double-stranded DNA library preparation (DSP). We also performed a single-stranded DNA library preparation (SSP) using mCRC patients and healthy control cirDNA, which allowed us to make the first ever end motif analysis in the literature which compares the use of DSP and SSP.

  Study EGAS50000001319

• Sequence data to study genomic CNVs that drive apoptotic resistance and relapses on immune checkpoint inhibitors

  This project investigates the genomic mechanisms underlying acquired resistance to immune checkpoint inhibitors (ICIs) across tumor types, addressing the critical clinical problem of treatment relapses where the molecular basis remains poorly understood. Through integrative genomic analyses of longitudinal clinical melanomas, functional CRISPR-Cas9 screens, and human and murine melanoma models, the study demonstrates that copy-number variant (CNV)-driven subclonal evolution is a primary driver of clinical relapses. The research identifies resistance-driver genes targeted by CNVs, including pro-apoptotic gene deletions and anti-apoptotic gene amplifications, which collectively downregulate apoptotic priming in resistant cells. The findings establish that modulating the apoptotic threshold can prevent or reverse ICI resistance, positioning CNV evolution as a key driver of acquired resistance and identifying apoptotic regulation as a therapeutic target to combat resistance evolution.

  Study EGAS50000001055

• Deregulation of FOXF1/FENDRR from t(14;16)(q32;q24) defines a subtype of high risk lineage ambiguous leukemia

  Despite great progress in understanding the genomic basis of immature T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL) and acute leukemias of ambiguous lineage (ALAL), there are still cases that lack defining genetic markers, complicating risk stratification and limiting targeted therapeutic options. Here, we describe a subtype of leukemia defined by the t(14;16)(q32;q24) translocation, which places the FOXF1 gene and its antisense long noncoding RNA gene FENDRR under the regulatory control of the BCL11B enhancer, leading to their ectopic transcriptional activation. Analysis of different high-throughput sequencing data, including WGS, RNA-seq, scDNA-seq, scRNA-seq, ChIP-seq, ATAC-seq, and HiChIP-seq, identified BCL11B-enhancer mediated deregulation of FOXF1/FENDRR as a hallmark of a subtype of high-risk lineage ambiguous leukemia that is potentially amenable to targeted therapeutic intervention.

  Study EGAS50000001255

• Spatiotemporal immune atlas of the first clinical-grade gene-edited pig-to-human kidney xenotransplant

  Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. We transplanted a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and studied the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells were uncommon in the porcine kidney cortex early after xenotransplantation and consisted of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages expressed genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft was detected. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression is sufficient to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.

  Study EGAS50000000244

• Single-cell RNA sequencing of 16 NPM1 mutated AML patients

  NPM1 mutated AML is the largest class in WHO classification, however several subtypes within NPM1 were already reported. Here, we sequence 16 NPM1 mutated AML samples with single-cell RNA-sequencing and multi-color flow cytometry from three major NPM1 subtypes we previously identified, totaling more than half a million cells. We show that the differences among three NPM1 subtypes are mainly driven by cell composition, and these differences are also reflected at cell surface protein level. With the re-analysis of CITE-seq data from another cohort and single cell variant calling on our data, we also report two distinct stem cell phenotypes: one with leukemic (CD34dimCD38-CD45RA+) and another with pre-leukemic (CD34+CD38-CD45RA-) origin. We believe that our data and findings provide novel insights regarding the etiology of NPM1 mutated AML.

  Study EGAS50000000332

• ALK inhibitors in the context of ALK-dependent cancer cell lines

  ALK inhibitors in the context of ALK-dependent cancer cell lines

  Dataset EGAD00001000078

• ChIIP-seq and RNA-seq

  epigenome profiling in tumor tissues and paired normal tissues of LUAD patients and transcriptome profiling in tumor tissues of LUAD patients.

  Dataset EGAD00001007066

• Pangenomic classification of pituitary adenomas

  Pituitary neuroendocrine tumors (PitNETs) are common. They are classified in five main histological types: PitNETs of POU1F1 (Pit1) lineage -lactotroph, somatotroph and thyrotroph -, gonadotroph, and corticotroph PitNETs. Pituitary tumorigenesis is poorly understood. We report here a pangenomic characterization of 134 PitNETs from all types, based on exome, genome, transcriptome, miRnome and methylome. Pit1 lineage was associated with a specific epigenetic signature of diffuse DNA hypomethylation, and correlated with expression of Pit1 markers and chromosomal instability. 45% of somatotroph PitNETs showed GNAS mutations. GNAS-wild type somatotroph showed a distinct transcriptome profile, expressing gonadotroph transcription factor NR5A1 (SF1). Sparsely granulated somatotroph PitNETs was classified apart from somatotroph, owing to a thyrotroph transcriptome signature. 43% of corticotroph PitNETs showed USP8 mutations, sharing a low epithelial-mesenchimal transition (EMT) transcriptome signature. Silent corticotroph PitNETs showed a gonadotroph transcriptome signature evoking transdifferentiation, and lost somatostatin target SSTR5 expression.

  Study EGAS00001003642

• Ongoing_mutagenesis_RNAseq

  One of the key questions to be explored is whether the biological processes generating specific mutational signatures continue to operate in the human cancer cell lines or simply reflect past mutagenic activity which is no longer operative. To address this question, we have extracted mutational signatures from 1,000 cancer cell lines of diverse cancer types. Several cell lines with mutational signatures of interest were selected, subcloned over a defined period of time and their genomes sequenced. The increased load of the mutations representative of a specific mutational signature within the genome of a subclone when compared to its parental clone was informative of the on-going mutational processes. To further study the recent observation that some of the clones belonging to a same cell line acquired differencet numbers of mutations over a set period of time, their RNA will be subjected to RNA-sequencing to study their differences.

  Study EGAS00001002364

• Evolutionary analysis of pancreatic cancer and coexistent precursor lesions using whole exome sequencing data

  Most adult carcinomas develop from noninvasive precursor lesions, a progression that is supported by genetic analysis. Further, the evolution of these lesions contextualizes the dynamics of advanced stage disease. We analyzed the somatic variants of co-existing pancreatic cancers and precursor lesions sampled from distinct regions of the same pancreas. After inferring evolutionary relationships, we found that the ancestral cell had initiated and clonally expanded to form one or more lesions, and that subsequent driver gene mutations eventually led to a pancreatic cancer. We also found that this multi-step progression generally spans many years. Our data suggest that independent, high-grade pancreatic lesions observed in a histologic cross section often represent a single neoplasm that can spread and colonize the ductal system, accumulating spatial and genetic divergence over time.

  Study EGAS00001002778

• Genomic DNA of tumor tissues, adjacent normal tissues, and peripheral blood were extracted using QIAamp DNA mini Kit (QIAGEN, cat. #51306)

  Although genomic instability, epigenetic abnormality, and gene expression dysregulation are hallmarks of colorectal cancer, these features have not been simultaneously analyzed at single cell resolution. Using optimized single cell multiomics sequencing together with multiregional sampling of the primary tumor, lymphatic and distant metastases, we provide insights beyond intratumoral heterogeneity. Genome wide DNA methylation levels were relatively consistent within a single genetic sublineage. The genome-wide DNA demethylation patterns of cancer cells were consistent in all 10 sequenced patients. The cancer cells’ DNA demethylation degrees clearly correlated with the densities of the heterochromatin-associated histone modification H3K9me3 of normal tissue, and those of repetitive element Long Interspersed Nuclear Element 1. Our work demonstrates the feasibility of reconstructing genetic lineages, and tracing their epigenomic and transcriptomic dynamics with single cell multiomics sequencing.

  Study EGAS00001003242

• Multi-omic single-cell profiling of peripheral blood immune cells from COVID-19 patients and controls.

  The COVID-19 pandemic, caused by SARS coronavirus 2 (SARS-CoV-2), has resulted in excess morbidity and mortality as well as economic decline. To characterise the systemic host immune response to SARS-CoV-2, we performed single-cell RNA-sequencing coupled with analysis of cell surface proteins, providing molecular profiling of over 800,000 peripheral blood mononuclear cells from a cohort of 130 patients with COVID-19. Our cohort, from three UK centres, spans the spectrum of clinical presentations and disease severities ranging from asymptomatic to critical. Three control groups were included: healthy volunteers, patients suffering from a non-COVID-19 severe respiratory illness and healthy individuals administered with intravenous lipopolysaccharide to model an acute inflammatory response. Full single cell transcriptomes are coupled with quantification of 188 cell surface proteins, and T and B lymphocyte antigen receptor repertoires.

  Study EGAS00001005465

• IYDP Indonesian Y chromosome Diversity Project

  Island Southeast Asia and Oceania host one of the world’s richest assemblages of human phenotypic, linguistic and cultural diversity. We compiled ~9.7 Mb of Y chromosome sequence from a diverse sample of over 380 men from this region, including 126 from Indonesian islands, first reported here. The granularity of this dataset allows us to fully resolve and date the regional Y chromosome phylogeny. This improved Y chromosome topology highlights localized events with important historical implications, including pre-Holocene contact between Mainland and Island Southeast Asia, ongoing interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape of today formed. The high-resolution phylogeny of the Y chromosome presented here thus enables a detailed exploration of past isolation, interaction and change in one of the world’s least understood regions.

  Study EGAS00001006028

• DNA methylation-based classification of sinonasal tumors [Proteomics data]

  The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent previously misclassified adenoid cystic carcinomas. The repository includes the raw mass spectrometry-based proteomics data

  Study EGAS00001006712

• DNA methylation-based classification of sinonasal tumors [DNA sequencing]

  The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent previously misclassified adenoid cystic carcinomas. This repository includes the results from DNA sequencing and mass spectrometry-based proteomics.

  Study EGAS00001006713